Achieving high sensitivity in mass spectrometry (MS) is key to effective analysis of complex chemical and biological samples. Every significant improvement in MS detection limits will enable applications that are otherwise impractical. Advances in MS sensitivity can also increase the dynamic range over which quantitative measurements can be performed.
FIG. 1 illustrates an electrospray ionization/mass spectrometer (ESI/MS) instrument configuration of a conventional design. In the figure, an atmospheric pressure electrospray ionization (ESI) source with an ES emitter couples to an ion funnel positioned in a low pressure (e.g., 18 Torr) region via a heated inlet capillary interface. Ions formed from electrospray at atmospheric pressure are introduced into the low pressure region through the capillary inlet and focused by the first ion funnel. A second ion funnel operating at a lower pressure (e.g., 2 Torr) than the first ion funnel operating pressure provides further focusing of ions prior to their introduction into a mass analyzer.
It well known in the art that sensitivity losses in ESI/MS are pronounced at the interface between the atmospheric pressure region and the low pressure region. Ion transmission through conventional interfaces is essentially limited by small MS sampling inlets—typically between 400 μm to 600 μm in diameter—required to maintain a good vacuum pressure in the MS analyzer. Sampling inlets can account for up to 99% of ion losses in the interface region, providing less than about 1% overall ion transmission efficiency. Accordingly, new systems, devices, and methods are needed to effectively eliminate the major ion losses in interface regions, e.g., between atmospheric ion source stage and a subsequent low pressure stage important to sensitive ion analyses.